title: Pseudovirus mimics cell entry and trafficking of the human polyomavirus JCPyV.
abstract: The normally asymptomatic human polyomavirus, JCPyV, is the causative agent of a rare but fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). Individuals at risk for developing PML include those with AIDS, with other underlying immunosuppressive diseases, and in patients treated with immunomodulatory regimens. Drugs to prevent viral reactivation in the setting of immunosuppression or immunomodulation could be used to sustain lives. Development of such drugs has been impeded by the difficulty of growing and studying the virus. We sought to develop a more efficient method for screening drugs that inhibit viral infection. Pseudovirus models have been developed which may be of use in pharmaceutical research. The use of pseudoviruses as models for viral infection is dependent on them using similar pathways for infection as virus. We screened known inhibitors of viral entry for their ability to block pseudovirus infection. Here we show that the pseudovirus based on the human polyomavirus JCPyV recapitulates virus binding, entry and trafficking. This system can be used for high-throughput screening of antiviral drugs.
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, United States.
authors.forename: Gretchen V
authors.initials: GV
authors.lastname: Gee
authors.forename: Bethany A
authors.initials: BA
authors.lastname: O'Hara
authors.forename: Aaron
authors.initials: A
authors.lastname: Derdowski
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Atwood
mesh_terms: D000998:Antiviral Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000502:physiology*; D014773:Virology / Q000379:methods*; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents
keywords: JC polyomavirus; Natalizumab; Progressive multifocal leukoencephalopathy; Pseudovirus; Virus entry